Actions of the Japanese Pancreas and Islet Transplantation Association regarding transplanted human islets isolated using Liberase HI.

Abstract

PURPOSE:

The potential for introducing transmissible spongiform encephalopathy (TSE) into islet cells was indicated by recognizing that Liberase HI is isolated from Clostridium histolyticum grown in media containing brain-heart infusion broth. A national team within the Japanese Pancreas and Islet Transplantation Association implemented an islet transplantation program in Japan using Liberase HI. The program comprised 65 islet isolations from non-heart-beating donors and 34 transplants into 18 patients. Herein, we have summarized how the Association followed these recipients over the long term.

PROCEDURES:

We established an ad hoc committee to follow recipients transplanted with islets isolated using Liberase HI after becoming informed of the associated dangers of using this enzyme. We also stopped islet transplantations using Liberase. The committee addressed the major concerns of the risk of the collagenase being contaminated with TSE and of the recipient follow-up. All recipients were examined by diffusion MRI and EEG and then scheduled for evaluation and follow-up by specialists in Creutzfeldt-Jakob disease (CJD). Bioassays of bovine spongiform encephalopathy prions in the enzyme proceeded using knock-in mice expressing bovine prion protein. These assays could detect contaminating prions at a dilution of 1 × 10(4). After inactivating its collagenase activity, Liberase HI was injected into the abdominal cavities of knock-in mice. Four months later, prion infectivity in Liberase HI was evaluated by immunohistochemical staining and Western blotting of spleen homogenates using anti-prion protein antibodies.

MAIN FINDINGS:

Western blotting and immunohistochemical staining did not detect prions in Liberase HI. Diffusion MRI and EEG evaluations performed by CJD specialists confirmed that none of the transplanted recipients had CJD.

CONCLUSIONS:

Three years of follow-up revealed that none of the Japanese recipients of islet transplants developed CJD. Prion bioassays showed that the Liberase HI used to isolate islets for transplantation was free of infectious TSE prions.

• Authors: T Saito, T Anazawa, M Gotoh, S Uemoto, T Kenmochi, Y Kuroda, S Satomi, T Itoh, Y Yasunami, T Kitamoto, S Mohri, S Teraoka
• Journal: Transplantation proceedings (Transplant Proc) Vol. 42 Issue 10 Pg. 4213-6 (Dec 2010) ISSN: 1873-2623 [Electronic] United States
• PMID: 21168667 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Collagenases
• Liberase
• Thermolysin

Topics

• Animals
• Blotting, Western
• Collagenases (administration & dosage)
• Immunohistochemistry
• Islets of Langerhans Transplantation (adverse effects)
• Japan
• Mice
• Prion Diseases (transmission)
• Societies, Medical
• Thermolysin (administration & dosage)